Flapjack: Data Management and Analysis for Genetic Circuit Characterization.

Flapjack presents a valuable solution for addressing challenges in the Design, Build, Test, Learn (DBTL) cycle of engineering synthetic genetic circuits. This platform provides a comprehensive suite of features for managing, analyzing, and visualizing kinetic gene expression data and associated metadata. By utilizing the Flapjack platform, researchers can effectively integrate the test phase with the build and learn phases, facilitating the characterization and optimization of genetic circuits. With its user-friendly interface and compatibility with external software, the Flapjack platform offers a practical tool for advancing synthetic biology research.This chapter provides an overview of the data model employed in Flapjack and its hierarchical structure, which aligns with the typical steps involved in conducting experiments and facilitating intuitive data management for users. Additionally, this chapter offers a detailed description of the user interface, guiding readers through accessing Flapjack, navigating its sections, performing essential tasks such as uploading data and creating plots, and accessing the platform through the pyFlapjack Python package.

Humoral immune response in people living with HIV after administration of SARS-CoV-2 vaccine CoronaVac or BNT162b2 or CoronaVac/BNT162b2 booster sequence: A cross-sectional study.

BACKGROUND: The evidence of SARS-CoV-2 vaccine effectiveness in people living with HIV (PLWH) is limited. This study evaluated the humoral immune response to CoronaVac™ (virus inactivated) and BNT162b2 (mRNA- based) vaccines in PLWH and HIV-negative controls, with and without a booster sequence. METHODS: We conducted a cross-sectional study on PLWH and HIV-negative controls who received CoronaVac or BNT162b2, with a subgroup receiving a CoronaVac/BNT162b2 booster. Blood samples were collected 4-6 months after primary vaccination and tested for anti-SARS-CoV-2 protein S (aSAb) and neutralizing antibodies (NtAb) using validated assays. Immune response was evaluated by age, sex, previous COVID-19 history, and CD4 + cell count. FINDINGS: One hundred and eighty nine participants were enrolled with 161 (85%) being PLWH. Among participants without previous known COVID-19, median aSAb levels were significantly lower in PLWH who received CoronaVac compared to BNT162b2 (32 U/mL vs. 587 U/mL, p < 0.001), with similar results in HIV-negative controls. NtAb presence was also significantly lower after CoronaVac compared to BNT162b2 (30% vs. 93%, p < 0.001). The booster sequence group showed a significant increase in aSAb titers in both PLWH and HIV-negative controls (from 33 U/ml to 2500 U/ml, p < 0.001), and NtAb positivity increased from 20% to 95 % in PLWH, and 27% to 100% in HIV-negative controls. Prior COVID-19 led to significantly higher post-vaccine antibody titers particularly in the BNT162b2 group. PLWH with CD4 + count < 200 cells/mL showed a weaker immune response to both vaccines. INTERPRETATION: CoronaVac resulted in a weaker immune response in both PLWH and HIV-negative controls compared to BNT162b2, particularly in immunosuppressed PLWH without prior COVID-19. Hybrid immunity and heterologous booster vaccination increased antibody levels. FUNDING: Local funding.

Learning to Live with HIV: The Experience of a Group of Young Chilean Men.

Young men aged 20-29 present the highest rates of HIV in Chile, yet little is known about their experiences after diagnosis. This study sheds light on the meaning of living with HIV for young gay Chilean males. Qualitative analysis of 11 in-depth interviews, employing Heidegger's hermeneutical approach, resulted in a depiction of feelings of loneliness and sadness, encounters with discrimination, and a lack of social support. Participants also offer recommendations on utilizing peer support as an essential component for programs targeting young gay men living with HIV in the capital of Chile. Additionally, they suggest that health care providers play a crucial role in supporting the process of accepting the condition. Conclusions: It is imperative to enhance psychological support by integrating it into the HIV program for all clients and families facing crisis situations. The establishment of support groups within hospitals that are part of the national program providers is recommended. Education on comprehensive sexuality should be provided in educational institutions, alongside visible campaigns across all media platforms to dismantle the stigma linked to the disease. Lastly, improvements in care duration and support from health services can be achieved through the provision of comprehensive care founded on unconditional acceptance.

Características clínicas y epidemiológicas de casos de viruela símica en personas que viven con VIH: análisis observacional

Antecedentes: La viruela del mono (mpox) es una zoonosis que se ha extendido rápida y globalmente desde mediados de 2022 y ha afectado mayoritariamente a hombres que tienen sexo con hombres (HSH). Objetivos: Caracterizar clínica y epidemiológicamente la infección por el virus mpox en personas que viven con VIH (PVVIH). Pacientes y Método: Se realizó un análisis clínico y epidemiológico a PVVIH que consultaron por sospecha de mpox en el Policlínico de Infectología del Hospital Clínico San Borja Arriarán. Se reportan los casos confirmados por reacción de polimerasa en cadena (RPC) entre el 11/07/2022 y 21/10/2022. Resultados: Se confirmó mpox en 35 pacientes, todos HSH y, la mayoría, en terapia antirretroviral. La mediana de edad fue 37 años. El promedio de días entre fase inicial sistémica inespecífica y eruptiva fue 1,7. Las lesiones fueron de tipo maculopapulares, costrosas y umbilicadas en las zonas genital, perianal, dorso y extremidades, mayoritariamente. Trece individuos presentaron complicaciones y dos requirieron hospitalización. De los con examen de VDRL solicitado, el 46,4% fue reactivo en títulos no residuales. Conclusiones: Se detectó llegada de mpox en un centro de atención de VIH en HSH en todos los niveles de estado inmune. Mayormente, los casos fueron leves a moderados y autolimitados. El cuadro clínico ha sido similar a lo descrito globalmente.

Background. Monkeypox (mpox) is a zoonosis that has spread rapidly and globally since mid-2022 and has mainly affected men who have sex with men (MSM). Aim: To characterize mpox clinically and epidemiologically in people living with HIV (PLHIV). Method: A clinical and epidemiological analysis was carried out on PLHIV who consulted for suspected mpox in the Infectious Disease clinic of the San Borja Arriarán Clinical Hospital. Cases confirmed by PCR are reported between 07/11/2022 and 10/21/2022. Results: Mpox was confirmed in 35 patients, all MSM and on antiretroviral therapy. The median age was 37 years. The average number of days between the initial non-specific systemic and eruptive phase was 1.7. The lesions were maculopapular, crusted, and umbilicated, mainly in the genital, perianal, back, and extremity areas. Thirteen patients presented complications and two required hospitalizations. Of those with a requested VDRL test, 46.4% were reactive in non-residual titers. Conclusions: Arrival of mpox was detected at the HIV care center in MSM at all levels of immune status. Mostly, the cases were mild to moderate and self-limiting. The clinical picture has been similar to that described globally.

An exploratory study of motivations for elective oocyte cryopreservation. / Estudio exploratorio de las motivaciones para la criopreservación de ovocitos en forma electiva.

Introduction: Oocyte vitrification is a scientific advance that has changed the reproductive perspective of human society. This procedure has been offered as an alternative to the voluntary postponement of pregnancy, giving women a new perspective on their reproductive autonomy. The number of women who consult and then choose to freeze oocytes has increased almost exponentially in Chile and throughout the world. There is little knowledge about the motivation, experience, and results of elective oocyte cryopreservation in Chile. The objective was to know the motivation, experience, and future reproductive desire of the women who underwent this technique. Methods: Cross-sectional descriptive study based on a questionnaire sent by e-mail in which females who had previously undergone elective oocyte cryopreservation between January 2011 and December 2019 at Clínica Alemana, Santiago, Chile, participated. Results: Of 342 women who had completed a cycle of elective oocyte cryopreservation, 193 agreed to participate, and of these, 98 (51%) answered the survey satisfactorily. Women who underwent this procedure for medical indication, including endometriosis, cancer, and low ovarian reserve, were excluded. The most frequent reason for the procedure was age (44%). Concerning the procedure: 94% do not regret having it done, and 74% of the women believe that they will use their oocytes at some point in their lives. Finally, from the time of oocyte cryopreservation to date, 11% of the surveyed women have used their vitrified oocytes, and 27% have become pregnant. Conclusions: Women who undergo elective oocyte cryopreservation for social reasons are mainly women without a partner whose main motivation is their reproductive age. The vast majority do not regret doing so.

Introducción: La vitrificación de óvulos es un avance científico que ha cambiado la perspectiva reproductiva de la sociedad humana. Este procedimiento se ha ofrecido como alternativa a la postergación voluntaria del embarazo, confiriéndole a la mujer una nueva perspectiva en su autonomía reproductiva. El número de mujeres que consultan y luego optan por congelar ovocitos ha aumentado en forma casi exponencial en Chile y en todo el mundo. En nuestro país, hay poco conocimiento acerca de la motivación, experiencia y resultados de la criopreservación electiva de ovocitos en Chile. El objetivo fue conocer la motivación, experiencia y el deseo reproductivo futuro de este grupo de mujeres sometidas a esta técnica. Métodos: Estudio descriptivo transversal, basado en un cuestionario enviado por correo electrónico en el que participaron mujeres que se habían sometido previamente a criopreservación electiva de ovocitos entre enero de 2011 y diciembre de 2019 en Clínica Alemana, Santiago de Chile. Resultados: De 342 mujeres que habían completado un ciclo de criopreservación electiva de ovocitos, 193 aceptaron participar y de estas, 98 (51%) de las mujeres contestaron la encuesta en forma satisfactoria. Se establecieron criterios de exclusión a aquellas mujeres que se habían sometido a este procedimiento por indicación médica como la endometriosis, el cáncer y la baja reserva ovárica. El motivo más frecuente para realizarse el procedimiento fue la edad (44%). En relación al procedimiento; el 94% no se arrepiente de haberlo realizado y 74% de las mujeres cree que utilizará sus ovocitos en algún momento de su vida. Por último, desde que se realizaron la criopreservación de ovocitos a la fecha, el 11% de las mujeres encuestadas ha usado sus ovocitos vitrificados y 27% ha logrado embarazarse con estos. Conclusión: Las mujeres que se someten a criopreservación electiva de ovocitos por razones sociales, son principalmente mujeres sin pareja que tiene como motivación principal su edad reproductiva y la gran mayoría de ellas no se arrepienten de haberlo realizado.

Estudio exploratorio de las motivaciones para la criopreservación de ovocitos en forma electiva / An exploratory study of motivations for elective oocyte cryopreservation

Introducción La vitrificación de óvulos es un avance científico que ha cambiado la perspectiva reproductiva de la sociedad humana. Este procedimiento se ha ofrecido como alternativa a la postergación voluntaria del embarazo, confiriéndole a la mujer una nueva perspectiva en su autonomía reproductiva. El número de mujeres que consultan y luego optan por congelar ovocitos ha aumentado en forma casi exponencial en Chile y en todo el mundo. En nuestro país, hay poco conocimiento acerca de la motivación, experiencia y resultados de la criopreservación electiva de ovocitos en Chile. El objetivo fue conocer la motivación, experiencia y el deseo reproductivo futuro de este grupo de mujeres sometidas a esta técnica. Métodos Estudio descriptivo transversal, basado en un cuestionario enviado por correo electrónico en el que participaron mujeres que se habían sometido previamente a criopreservación electiva de ovocitos entre enero de 2011 y diciembre de 2019 en Clínica Alemana, Santiago de Chile. Resultados De 342 mujeres que habían completado un ciclo de criopreservación electiva de ovocitos, 193 aceptaron participar y de estas, 98 (51%) de las mujeres contestaron la encuesta en forma satisfactoria. Se establecieron criterios de exclusión a aquellas mujeres que se habían sometido a este procedimiento por indicación médica como la endometriosis, el cáncer y la baja reserva ovárica. El motivo más frecuente para realizarse el procedimiento fue la edad (44%). En relación al procedimiento; el 94% no se arrepiente de haberlo realizado y 74% de las mujeres cree que utilizará sus ovocitos en algún momento de su vida. Por último, desde que se realizaron la criopreservación de ovocitos a la fecha, el 11% de las mujeres encuestadas ha usado sus ovocitos vitrificados y 27% ha logrado embarazarse con estos. Conclusión Las mujeres que se someten a criopreservación electiva de ovocitos por razones sociales, son principalmente mujeres sin pareja que tiene como motivación principal su edad reproductiva y la gran mayoría de ellas no se arrepienten de haberlo realizado.

Introduction Oocyte vitrification is a scientific advance that has changed the reproductive perspective of human society. This procedure has been offered as an alternative to the voluntary postponement of pregnancy, giving women a new perspective on their reproductive autonomy. The number of women who consult and then choose to freeze oocytes has increased almost exponentially in Chile and throughout the world. There is little knowledge about the motivation, experience, and results of elective oocyte cryopreservation in Chile. The objective was to know the motivation, experience, and future reproductive desire of the women who underwent this technique. Methods Cross-sectional descriptive study based on a questionnaire sent by e-mail in which females who had previously undergone elective oocyte cryopreservation between January 2011 and December 2019 at Clínica Alemana, Santiago, Chile, participated. Results Of 342 women who had completed a cycle of elective oocyte cryopreservation, 193 agreed to participate, and of these, 98 (51%) answered the survey satisfactorily. Women who underwent this procedure for medical indication, including endometriosis, cancer, and low ovarian reserve, were excluded. The most frequent reason for the procedure was age (44%). Concerning the procedure: 94% do not regret having it done, and 74% of the women believe that they will use their oocytes at some point in their lives. Finally, from the time of oocyte cryopreservation to date, 11% of the surveyed women have used their vitrified oocytes, and 27% have become pregnant. Conclusions Women who undergo elective oocyte cryopreservation for social reasons are mainly women without a partner whose main motivation is their reproductive age. The vast majority do not regret doing so.

Improvement of Advanced Sample Preparation Systems for the Determination of Trace Ni in Seawater by Electro-Membranes.

Due to its important environmental role, the analysis of trace metals in natural waters is attracting increasing attention; consequently, faster and more accurate analytical methods are now needed to reach even lower limits of detection. In this work, we propose the use of electro-membrane extraction (EME) to improve analytical methods based on hollow fiber liquid phase micro-extraction (HFLPME). Specifically, an EME-based method for the determination of trace Ni in seawater has been developed, using an HFLPME system with di-2-ethylhexyl phosphoric acid (DEHPA) in kerosene as a chemical carrier, followed by instrumental determination by graphite furnace atomic absorption spectroscopy (GFAAS). Under optimum conditions, Ni was pre-concentrated 180 ± 17 times after 15 min, using sample pH = 5.5, the concentration of DEHPA 0.9 M in the liquid membranes, and 1.9 M HNO3 in the acceptor solution, as well as an electric potential of 25 V with the sample being stirred at 500 rpm. When compared with other HFLPME systems for pre-concentration of trace Ni in seawater in the absence of electric potential, the enrichment factor was improved 2.2 times, while the time of extraction was reduced an 89%. The limit of detection of the new method was 23.3 ng L-1, and both its applicability and accuracy were successfully evaluated by analyzing Ni concentration in a seawater-certified reference material (BCR-403), showing the reliability of EME for sample preparation in the determination of trace metals in marine water samples.

Mpox in people with advanced HIV infection: a global case series.

BACKGROUND: People living with HIV have accounted for 38-50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). METHODS: A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. FINDINGS: We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30-43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117-291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100-200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance. INTERPRETATION: A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death. FUNDING: None.

An electromembrane microextraction-based green method for the determination of trace copper in natural waters.

Driven by the search for an environmentally-friendly methodology, electromembrane extraction (EME) has recently emerged as a green and versatile tool for the analysis of trace pollutants in water samples, being mainly applied to the preconcentration and determination of organic compounds. Recently, EME has also shown its applicability to the analysis of inorganic species, allowing a considerable reduction in both reagent consumption and extraction times, and without loss of efficacy, in comparison with other liquid phase microextraction techniques. In this study, an EME system for trace copper analysis in natural waters has been optimised by the modified simplex method. A chemical modifier, di-2-pyridyl ketone benzoylhydrazone (dPKBH) was synthesized and dissolved in 1-nonanol, to be used as an organic phase impregnated into the pores of a polymeric hollow fibre. With only 15 min of extraction, an enrichment factor of 77.1 ± 10.8 was obtained for a wide salinity range (0-35), allowing its application in a variety of different waters, including seawater. Optimum operating conditions were a sample pH of 6.26, an electric potential of 95 V, 0.08 M nitric acid as the acceptor phase, 4.01 mM dPKBH in 1-nonanol as the organic phase and a stirring rate of 1500 rpm. A LOD of 0.004 µg L-1 was obtained, and the system was successfully applied to the analysis of several water samples containing copper at low ppb levels (tap water and river water) or even at sub-ppb levels (seawater).

Accurate characterization of dynamic microbial gene expression and growth rate profiles.

Genetic circuits are subject to variability due to cellular and compositional contexts. Cells face changing internal states and environments, the cellular context, to which they sense and respond by changing their gene expression and growth rates. Furthermore, each gene in a genetic circuit operates in a compositional context of genes which may interact with each other and the host cell in complex ways. The context of genetic circuits can, therefore, change gene expression and growth rates, and measuring their dynamics is essential to understanding natural and synthetic regulatory networks that give rise to functional phenotypes. However, reconstruction of microbial gene expression and growth rate profiles from typical noisy measurements of cell populations is difficult due to the effects of noise at low cell densities among other factors. We present here a method for the estimation of dynamic microbial gene expression rates and growth rates from noisy measurement data. Compared to the current state-of-the-art, our method significantly reduced the mean squared error of reconstructions from simulated data of growth and gene expression rates, improving the estimation of timing and magnitude of relevant shapes of profiles. We applied our method to characterize a triple-reporter plasmid library combining multiple transcription units in different compositional and cellular contexts in Escherichia coli. Our analysis reveals cellular and compositional context effects on microbial growth and gene expression rate dynamics and suggests a method for the dynamic ratiometric characterization of constitutive promoters relative to an in vivo reference.

[SARS-CoV-2 infection in people living with HIV. Topics on the global panorama and in Chile]. / Infección por SARS-CoV-2 en personas viviendo con VIH. Tópicos del panorama mundial y en Chile.

The COVID-19 disease is caused by the SARS-CoV-2 virus and was declared a pandemic by the WHO on March 11, 2020. To date, more than 500 million people have been infected and it has caused over 6 million deaths worldwide. People that belong to the most vulnerable risk groups, such as those at the extremes of life, patients with chronic comorbidities and those with severe immunosuppression, are especially susceptible to developing a severe form of COVID-19 infection and death. Subjects living with HIV, especially those in precarious immunological conditions or those in whom antiretroviral therapy is yet to be started, may be at risk of developing complications related to COVID-19, as observed with other infectious diseases. This review aims to determine the magnitude of the impact of the SARS-CoV-2 virus on people living with HIV in Chile.

Infección por SARS-CoV-2 en personas viviendo con VIH: tópicos del panorama mundial y en Chile / SARS-CoV-2 infection in people living with HIV: topics on the global panorama and in Chile

Resumen La enfermedad COVID-19 es una patología de origen infeccioso causada por el virus SARS-CoV-2 y fue declarada pandemia por la OMS el 11 de marzo 2020. A la fecha se registran más de 500 millones de personas infectadas y más de 6 millones de fallecidos en todo el mundo. Las personas que pertenecen a grupos de riesgo más vulnerables, particularmente aquellos que se encuentran en los extremos de la vida, con comorbilidades crónicas o inmunocomprometidas, son especialmente susceptibles a presentar un eventual mayor riesgo de infección, de gravedad y de mortalidad por esta enfermedad. Las personas que viven con VIH, especialmente aquellos en precarias condiciones inmunológicas o aquellas que aún no inician terapia antiretroviral, pueden ser un grupo especialmente susceptible de presentar complicaciones relacionadas a esta y otras enfermedades de origen infeccioso. Con esta revisión se pretende determinar la magnitud del impacto del virus SARS-CoV-2 en personas viviendo con VIH en Chile.

Abstract The COVID-19 disease is caused by the SARS-CoV-2 virus and was declared a pandemic by the WHO on March 11, 2020. To date, more than 500 million people have been infected and it has caused over 6 million deaths worldwide. People that belong to the most vulnerable risk groups, such as those at the extremes of life, patients with chronic comorbidities and those with severe immunosuppression, are especially susceptible to developing a severe form of COVID-19 infection and death. Subjects living with HIV, especially those in precarious immunological conditions or those in whom antiretroviral therapy is yet to be started, may be at risk of developing complications related to COVID-19, as observed with other infectious diseases. This review aims to determine the magnitude of the impact of the SARS-CoV-2 virus on people living with HIV in Chile.

Analytical Performance of Electromembranes as a Tool for Nanoconcentrations of Silver in Waters.

Electromembranes increase the efficiency of metal transport in liquid-phase microextraction systems by applying an electric potential, which accelerates the transport. Nevertheless, to get high extraction percentages in short extraction times it is necessary to take into account a great variety of factors, and multivariate optimization techniques are the best alternative to determine the most influential variables and to optimize the extraction process. In this work, a fractional factorial design was applied to determine the most influential variables in the extraction of silver by electromembranes. Thus, the effect of tri-isobutylphosphine sulphide (Cyanex 471x) concentration in the organic solution, sodium thiosulphate concentration in the acceptor solution, nitrate concentration in the sample solution, extraction time, stirring rate and electric potential on the enrichment factor were studied. Once the most important variables were selected, a small composite design (Draper-Lin) was used to obtain their optimal values to maximize the enrichment factor. Under these conditions, an experimental enrichment factor of 49.91 ± 3.95 was achieved after 22 min. Finally, the effect of saline matrix on the enrichment factor was tested and the optimized system was successfully applied to analyse silver concentrations at ultratrace levels, within the range of 7-29 ng·L-1 in different real seawater samples.

Recomendaciones para el diagnóstico y el manejo de la infección por citomegalovirus en la mujer embarazada y el recién nacido / Recommendations for the diagnosis and management of cytomegalovirus infection in pregnant women and newborns

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la infección por citomegalovirus (CMV) en la mujer embarazada y el recién nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por CMV en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.

Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnancy and Newborn. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation, diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.

Recomendaciones para el diagnóstico y manejo de la infección por citomegalovirus en la mujer embarazada y el recién nacido / Recommendations for the diagnosis and management of cytomegalovirus infection in pregnant woman and newborn infant

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la Infección por Citomegalovirus en la Mujer Embarazada y el Recién Nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por citomegalovirus (CMV) en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.

Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnant Woman and Newborn Infant. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation; diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.

Clinical characteristics and outcomes of people living with HIV hospitalized with COVID-19: a nationwide experience.

In this prospective, multicentric, observational study, we describe the clinical characteristics and outcomes of people living with HIV (PLHIV) requiring hospitalization due to COVID-19 in Chile and compare them with Chilean general population admitted with SARS-CoV-2. Consecutive PLHIV admitted with COVID-19 in 23 hospitals, between 16 April and 23 June 2020, were included. Data of a temporally matched-hospitalized general population were used to compare demography, comorbidities, COVID-19 symptoms, and major outcomes. In total, 36 PLHIV subjects were enrolled; 92% were male and mean age was 44 years. Most patients (83%) were on antiretroviral therapy; mean CD4 count was 557 cells/mm3. Suppressed HIV viremia was found in 68% and 56% had, at least, one comorbidity. Severe COVID-19 occurred in 44.4%, intensive care was required in 22.2%, and five patients died (13.9%). No differences were seen between recovered and deceased patients in CD4 count, HIV viral load, or time since HIV diagnosis. Hypertension and cardiovascular disease were associated with a higher risk of death (p = 0.02 and 0.006, respectively). Compared with general population, the HIV cohort had significantly more men (OR 0.15; IC 95% 0.07-0.31) and younger age (OR 8.68; IC 95% 2.66-28.31). In PLHIV, we found more intensive care unit admission (OR 2.31; IC 95% 1.05-5.07) but no differences in the need for mechanical ventilation or death. In this cohort of PLHIV hospitalized with COVID-19, hypertension and cardiovascular comorbidities, but not current HIV viro-immunologic status, were the most important risk factors for mortality. No differences were found between PLHIV and general population in the need for mechanical ventilation and death.

Role and effects of zinc supplementation in HIV-infected patients with immunovirological discordance: A randomized, double blind, case control study.

INTRODUCTION: It has been estimated that between 15% and 18% of patients who start antiretroviral therapy (ART) do not achieve a successful immune recovery despite complete virological suppression. In the literature this phenomenom is known as poor immune recovery or immunovirological discordance (IVD). Zinc has an immunomodulatory role associated with T lymphocytes and its supplementation could enhance immune recovery. OBJECTIVE: To determine if zinc supplementation on IVD patients prevents immune failure after 12 months of supplementation. Secondary objectives were to determine serum zinc levels in HIV patients with and without IVD and the frequency of hypozincemia in discordant patients. METHOD: We reviewed the historical record of patients under care at Arriarán Foundation. Following inclusion criteria were defined: 1) age ≥ 18 years, 2) standard ART (three effective drugs) for at least 18 months, 3) virologically suppressed for 12 months, 3) persistence of CD4 count ≤200 cells/mm3 and/or increase ≤ 80 cells/mm3 after one year of viral undetectability. A control group was assigned paired 1:1 by sex, age (± 2 years) that did achieved an increase of CD4> 350 cells/ mm3. In both groups plasma zinc levels were determined. In a later phase, patients with IVD were randomized to receive zinc (15 mg daily) versus placebo. Patients were followed for 12 months with CD4 count, viral load and zinc levels determinations every 4-6 months. RESULTS: A total of 80 patients, 40 patients with IVD criteria and 40 controls were included. 92.5% were men, and age average was 47.5 years. The median baseline CD4 was 189 cells/mm3 (71-258) in the cases vs. 552.5 cells/ mm3 (317-400) in the control group with a median increase at the end of the study of 39 cell/mm3 and 19 cell/mm3 respectively. There was no difference in baseline plasma zinc levels between both groups (81.7 + 18.1 in cases versus 86.2 + 11.0 in controls). In the 40 patients with IVD, the median absolute increase in CD4 after annual zinc supplementation was 31.5 cells/mm3 in the treated group versus 50 cells/mm3 in the placebo group, this difference being statistically not significant (p = 0.382). CONCLUSIONS: Patients with IVD have plasma zinc levels similar to those who achieve adequate immune recovery. Zinc supplementation in IVD patients showed a statistically non-significant difference in in CD4 levels between cases and controls. The results warrant a comparative study with a larger number of patients.

[Recommendations for the diagnosis and management of cytomegalovirus infection in pregnant woman and newborn infant]. / Recomendaciones para el diagnóstico y manejo de la infección por citomegalovirus en la mujer embarazada y el recién nacido.

The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnant Woman and Newborn Infant. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation; diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.

Flapjack: Data Management and Analysis for Genetic Circuit Characterization.

Characterization is fundamental to the design, build, test, learn (DBTL) cycle for engineering synthetic genetic circuits. Components must be described in such a way as to account for their behavior in a range of contexts. Measurements and associated metadata, including part composition, constitute the test phase of the DBTL cycle. These data may consist of measurements of thousands of circuits, measured in hundreds of conditions, in multiple assays potentially performed in different laboratories and using different techniques. In order to inform the learn phase this large volume of data must be filtered, collated, and analyzed. Characterization consists of using this data to parametrize models of component function in different contexts, and combining them to predict behaviors of novel circuits. Tools to store, organize, share, and analyze large volumes of measurement and metadata are therefore essential to linking the test phase to the build and learn phases, closing the loop of the DBTL cycle. Here we present such a system, implemented as a web app with a backend data registry and analysis engine. An interactive frontend provides powerful querying, plotting, and analysis tools, and we provide a REST API and Python package for full integration with external build and learn software. All measurements are associated with circuit part composition via SBOL (Synthetic Biology Open Language). We demonstrate our tool by characterizing a range of genetic components and circuits according to composition and context.

Novel Tunable Spatio-Temporal Patterns From a Simple Genetic Oscillator Circuit.

Multicellularity, the coordinated collective behavior of cell populations, gives rise to the emergence of self-organized phenomena at many different spatio-temporal scales. At the genetic scale, oscillators are ubiquitous in regulation of multicellular systems, including during their development and regeneration. Synthetic biologists have successfully created simple synthetic genetic circuits that produce oscillations in single cells. Studying and engineering synthetic oscillators in a multicellular chassis can therefore give us valuable insights into how simple genetic circuits can encode complex multicellular behaviors at different scales. Here we develop a study of the coupling between the repressilator synthetic genetic ring oscillator and constraints on cell growth in colonies. We show in silico how mechanical constraints generate characteristic patterns of growth rate inhomogeneity in growing cell colonies. Next, we develop a simple one-dimensional model which predicts that coupling the repressilator to this pattern of growth rate via protein dilution generates traveling waves of gene expression. We show that the dynamics of these spatio-temporal patterns are determined by two parameters; the protein degradation and maximum expression rates of the repressors. We derive simple relations between these parameters and the key characteristics of the traveling wave patterns: firstly, wave speed is determined by protein degradation and secondly, wavelength is determined by maximum gene expression rate. Our analytical predictions and numerical results were in close quantitative agreement with detailed individual based simulations of growing cell colonies. Confirming published experimental results we also found that static ring patterns occur when protein stability is high. Our results show that this pattern can be induced simply by growth rate dilution and does not require transition to stationary phase as previously suggested. Our method generalizes easily to other genetic circuit architectures thus providing a framework for multi-scale rational design of spatio-temporal patterns from genetic circuits. We use this method to generate testable predictions for the synthetic biology design-build-test-learn cycle.